Serum Oxidative Stress Marker Levels in Unmedicated and Medicated Patients with Schizophrenia

Abstract

Oxidative stress has been suggested to be involved in schizophrenia, but studies have demonstrated inconsistent results on oxidative stress marker level/activity in patients with schizophrenia. In order to clarify the circulating oxidative stress marker level/activity in patients with schizophrenia, this study recruited 80 schizophrenia patients (40 first-episode, drug-free and 40 chronically medicated patients) and 80 controls to analyze serum activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), and levels of lipid peroxidation marker malondialdehyde (MDA) in schizophrenia patients, and whether they associate with the severity of the disease. We showed that only serum GSH-Px activity was significantly reduced in unmedicated patients with schizophrenia when compared with control subjects, whereas the other three analyzed oxidative stress markers did not show significant differences between cases and controls. Moreover, our results demonstrated that chronic medication increased GSH-Px activity and MDA levels in patients with schizophrenia, but reduced SOD activity in the patients. We also found that short-term antipsychotic treatments on the patients with schizophrenia reduced the SOD activity. Correlation analyses indicated that the oxidative stress marker activity/level is not significantly associated with the severity of schizophrenia, except that SOD level correlated with PANSS positive score significantly. Taken together, the data from the present study suggested that the dysfunctions of oxidative stress markers in patients with schizophrenia were mainly caused by antipsychotics, emphasizing increased oxidative stress as a potential side effect of antipsychotics on the patients.

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References

  1. Abdel-Salam OM, Youness ER, Mohammed NA, Morsy SM, Omara EA, Sleem AA (2014) Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice. J Med Food 17(5):588–598

    CAS  Article  Google Scholar 

  2. Akyol O, Herken H, Uza E, Fadıllıog E, Ozyurta H, Savas HA (2002) The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. Prog Neuro-Psychopharmacol Biol Psychiatry 26:995–1005

    CAS  Article  Google Scholar 

  3. Ben Othmen L, Mechri A, Fendri C et al (2008) Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings. Prog Neuro-Psychopharmacol Biol Psychiatry 32(1):155–159

    CAS  Article  Google Scholar 

  4. Boskovic M, Grabnar I, Terzic T, Kores Plesnicar B, Vovk T (2013) Oxidative stress in schizophrenia patients treated with long-acting haloperidol decanoate. Psychiatry Res 210(3):761–768

    CAS  Article  Google Scholar 

  5. Dadheech G, Mishra S, Gautam S, Sharma P (Sep 2006) Oxidative stress, alpha-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem 21(2):34–38

    CAS  Article  Google Scholar 

  6. Do KQ, Trabesinger AH, Kirsten-Kruger M et al (2000) Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo. Eur J Neurosci 12(10):3721–3728

    CAS  Article  Google Scholar 

  7. Dzul-Caamal R, Salazar-Coria L, Olivares-Rubio HF, Rocha-Gomez MA, Giron-Perez MI, Vega-Lopez A (Oct 2016) Oxidative stress response in the skin mucus layer of Goodea gracilis (Hubbs and Turner, 1939) exposed to crude oil: a non-invasive approach. Comp Biochem Physiol A Mol Integr Physiol 200:9–20

    CAS  Article  Google Scholar 

  8. Gawryluk JW, Wang JF, Andreazza AC, Shao L, Young LT (2011) Decreased levels of glutathione, the major brain antioxidant, in post-mortem prefrontal cortex from patients with psychiatric disorders. Int J Neuropsychopharmacol 14(1):123–130

    CAS  Article  Google Scholar 

  9. Grignon S, Chianetta JM (2007) Assessment of malondialdehyde levels in schizophrenia: a meta-analysis and some methodological considerations. Prog Neuro-Psychopharmacol Biol Psychiatry 31:365–369

    CAS  Article  Google Scholar 

  10. Guzelhan Y, Sayar K, Ozturk M, Kara I (2000) Free radicals in schizophrenia. Bull Clin Psycophamacol

  11. Herken H, Uz E, Ozyurt H, Sogut S, Virit O, Akyol O (2001) Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psychiatry 6:66–73

    CAS  Article  Google Scholar 

  12. Kubrak OI, Husak VV, Rovenko BM, Storey JM, Storey KB, Lushchak VI (Oct 2011) Cobalt-induced oxidative stress in brain, liver and kidney of goldfish Carassius auratus. Chemosphere 85(6):983–989

    CAS  Article  Google Scholar 

  13. Kuloglu M, Ustundag B, Atmaca M, Canatan H, Ertan Tezcan A, Cinkilinc N (2002a) Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct 20:171–175

    CAS  Article  Google Scholar 

  14. Kuloglu M, Ustundag B, Atmaca M, Canatan H, Tezcan AE, Cinkilinc N (Jun 2002b) Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder. Cell Biochem Funct 20(2):171–175

    CAS  Article  Google Scholar 

  15. Kunz M, Gama CS, Andreazza AC, Salvador M, Ceresér KM, Gomes FA, Belmonte-de-Abreu PS, Berk M, Kapczinski F (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuro-Psychopharmacol Biolog Psychiatry 32:1677–1681

    CAS  Article  Google Scholar 

  16. Mahadik SP, Scheffer RE (1996) Oxidative injury and potential use of antioxidants in schizophrenia. Prostaglandins Leukot Essent Fat Acids 55(1–2):45–54

    CAS  Article  Google Scholar 

  17. Mahadik SP, Pillai A, Joshi S, Foster A (2006) Prevention of oxidative stress-mediated neuropathology and improved clinical outcome by adjunctive use of a combination of antioxidants and omega-3 fatty acids in schizophrenia. Int Rev Psychiatry 18(2):119–131

    Article  Google Scholar 

  18. Meena Arvindakshan SS, Debsikdar V, Ghate M, Evans D, Horrobin DF, Bennett C, Ranjekar PK, Mahadik SP (2003) Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Biol Psychiatry 53(1):56–64

    Article  Google Scholar 

  19. Morera-Fumero AL, Diaz-Mesa E, Abreu-Gonzalez P, Fernandez-Lopez L, Cejas-Mendez MD (2017) Low levels of serum total antioxidant capacity and presence at admission and absence at discharge of a day/night change as a marker of acute paranoid schizophrenia relapse. Psychiatry Res 249:200–205

    CAS  Article  Google Scholar 

  20. Mukherjee S, Mahadik SP, Scheffer R, Correnti EE, Kelkar H (1996) Impaired antioxidant defense at the onset of psychosis. Schizophr Res 19(1):19–26

    Article  Google Scholar 

  21. Oruc EO, Sevgiler Y, Uner N (2004) Tissue-specific oxidative stress responses in fish exposed to 2,4-D and azinphosmethyl. Comp Biochem Physiol Toxicol Pharmacol 137(1):43–51

    Article  Google Scholar 

  22. Otunola GA, Oloyede OB, Oladiji AT, Afolayan AJ (2014) Selected spices and their combination modulate hypercholesterolemia-induced oxidative stress in experimental rats. Biol Res 47:5

    PubMed  PubMed Central  Google Scholar 

  23. Pomierny-Chamiolo L, Moniczewski A, Wydra K, Suder A, Filip M (Jan 2013) Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine. Neurotox Res 23(1):92–102

    CAS  Article  Google Scholar 

  24. Raffa M, Barhoumi S, Atig F, Fendri C, Kerkeni A, Mechri A (2012) Reduced antioxidant defense systems in schizophrenia and bipolar I disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 39(2):371–375

    CAS  Article  Google Scholar 

  25. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 121(2):109–122

    CAS  Article  Google Scholar 

  26. Reddy R, Sahebarao MP, Mukherjee S, Murthy JN (1991) Enzymes of the antioxidant defense system in chronic schizophrenic patients. Biol Psychiatry 30(4):409–412

    CAS  Article  Google Scholar 

  27. Rukmini MS, D'Souza B, D'Souza V (Jul 2004) Superoxide dismutase and catalase activities and their correlation with malondialdehyde in schizophrenic patients. Indian J Clin Biochem 19(2):114–118

    CAS  Article  Google Scholar 

  28. Sarandol A, Kirli S, Akkaya C, Altin A, Demirci M, Sarandol E (2007) Oxidative-antioxidative systems and their relation with serum S100 B levels in patients with schizophrenia: effects of short term antipsychotic treatment. Prog Neuro-Psychopharmacol Biol Psychiatry 31(6):1164–1169

    CAS  Article  Google Scholar 

  29. Skinner AO, Mahadik SP, Garver DL (2005) Thiobarbituric acid reactive substances in the cerebrospinal fluid in schizophrenia. Schizophr Res 76(1):83–87

    Article  Google Scholar 

  30. Sorokin AM, Moiseeva NB, Cheredeev AN, Frolova IS (1988) The interferon-natural killer cell system of patients with ovarian tumors. Akush Ginekol (Mosk) (5):23–27

  31. Wang P, Xie K, Wang C, Bi J (2014) Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis. Eur Neurol 72(3–4):249–254

    CAS  Article  Google Scholar 

  32. Yao JK, Reddy R, McElhinny LG, van Kammen DP (1998) Effects of haloperidol on antioxidant defense system enzymes in schizophrenia. J Psychiatr Res 32(6):385–391

    CAS  Article  Google Scholar 

  33. Zhang XY, Tan YL, Cao LY, Wu GY, Xu Q, Shen Y, Zhou DF (2006) Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophr Res 81(2–3):291–300

    Article  Google Scholar 

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Funding

This study was supported by the National Science Foundation of China (81703492), Beijing Natural Science Foundation (7182092), the Minzu University Research Fund (2018CXTD03), and the MUC 111 project.

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Correspondence to Yong Cheng.

Ethics declarations

Before inclusion in this study, all participants gave written informed consent. The study protocol has been approved by the Ethics Committee at The Third Hospital of Fuoshan, Fuoshan, China, and the experiments were conducted in accordance with the Declaration of Helsinki.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Cite this article

Bai, Z., Li, X., Chen, G. et al. Serum Oxidative Stress Marker Levels in Unmedicated and Medicated Patients with Schizophrenia. J Mol Neurosci 66, 428–436 (2018). https://doi.org/10.1007/s12031-018-1165-4

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Keywords

  • Schizophrenia
  • Antipsychotics
  • Oxidative stress
  • Superoxide dismutase
  • Glutathione peroxidase
  • Total antioxidant capacity
  • Malondialdehyde